Carbohydrate antigen 19-9 as a novel prognostic biomarker in distal cholangiocarcinoma

Abstract

Background: Distal cholangiocarcinoma (DCC) presents as one of the relatively rare malignant tumors in the digestive system and has a poor long-term prognosis. Curative resection is currently the most appropriate therapy for patients with DCC because of the lack of effective adjuvant therapies. Therefore, it is important to accurately predict the prognosis for formulating a reasonable treatment plan and avoiding unnecessary surgical trauma.

Aim: To minimize the interference of obstructive jaundice on carbohydrate antigen 19-9 (CA19-9) level by adapting CA19-9 to γ-glutamyltransferase (GGT) as an indicator, to determine the strong associations between CA19-9/GGT and postoperative neoplasm recurrence and long-term outcome of DCC.

Methods: We enrolled 186 patients who were diagnosed with DCC between January 2010 and December 2019 and performed radical excision with strict criteria as follows in our hospital. Receiver operating characteristic curves were drawn according to preoperative CA19-9/GGT and 1-year survival. Based on this, patients were divided into two groups (group 1, low-ratio, n = 81; group 2, high-ratio, n = 105). Afterwards, by the way of univariate and multivariate analysis, the risk factors influencing postoperative tumor recrudesce and long-term prognosis of patients with DCC were screened out.

Results: Optimum cut-off value of CA19-9/GGT was 0.12. Patients in group 2 represented higher CA19-9 and lymphatic metastasis rate accompanied by lower GGT, when compared with group 1 (P < 0.05). The 1-, 3- and 5-year overall survival rates of patients in groups 1 and 2 were 88.3%, 59.2% and 48.1%, and 61.0%, 13.6% and 13.6%, respectively (P = 0.000). Multivariate analysis indicated that CA19-9/GGT, lymphatic metastasis and tumor differentiation were independent risk factors for tumor recurrence and long-term prognosis of DCC.

Conclusion: Elevation of CA19-9/GGT performed better as a biomarker of aggressive carcinoma and predictor of poor clinical outcomes by reducing the effect of obstruction of biliary tract on CA19-9 concentration in patients with DCC.

Keywords: Carbohydrate antigen 19-9; Distal cholangiocarcinoma; Pancreaticoduodenectomy; Prognosis; Relapse; γ-Glutamyltransferase.

Figure 1

Screening flow chart. DCC: distal cholangiocarcinoma; PHC: primary hepatic carcinoma.

Figure 2

Time-dependent receiver operating characteristic curve. The area under curve of the carbohydrate antigen 19-9 to γ-glutamyltransferase ratio to predict the 1-year overall survival was 0.695.

Figure 3

Long-term prognosis of the patients with distal cholangiocarcinoma. A: Overall DFS curve of patients; B: OS curve of patients. DFS: disease-free survival; OS: overall survival.

Figure 4

Overall long-term prognosis between two groups in patients with distal cholangiocarcinoma. A: Overall disease-free survival curve of two groups of patients; B: Overall survival curve of two groups of patients. CA19-9: carbohydrate antigen 19-9; GGT: γ-glutamyltransferase.